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Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women

Author

Listed:
  • Latha Kadalayil

    (University of Southampton, Southampton General Hospital
    University of Southampton, Highfield Campus)

  • Sofia Khan

    (University of Helsinki and Helsinki University Hospital)

  • Heli Nevanlinna

    (University of Helsinki and Helsinki University Hospital)

  • Peter A. Fasching

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN)

  • Fergus J. Couch

    (Mayo Clinic)

  • John L. Hopper

    (The University of Melbourne, Melbourne)

  • Jianjun Liu

    (Genome Institute of Singapore
    National University of Singapore, 12 Science Drive 2)

  • Tom Maishman

    (University of Southampton and University Hospital Southampton NHS Foundation Trust)

  • Lorraine Durcan

    (University of Southampton and University Hospital Southampton NHS Foundation Trust)

  • Sue Gerty

    (University of Southampton and University Hospital Southampton NHS Foundation Trust)

  • Carl Blomqvist

    (Helsinki University Central Hospital)

  • Brigitte Rack

    (University Ulm, Prittwitzstrasse 43)

  • Wolfgang Janni

    (University Ulm, Prittwitzstrasse 43)

  • Andrew Collins

    (University of Southampton, Southampton General Hospital)

  • Diana Eccles

    (University of Southampton, Southampton University Hospitals NHS Trust)

  • William Tapper

    (University of Southampton, Southampton General Hospital)

Abstract

To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2315 patients aged ≤ 40 years at diagnosis. Here, we identify two SNPs associated with early-onset DFS, rs715212 (P meta = 3.54 × 10−5) and rs10963755 (P meta = 3.91 × 10−4) in ADAMTSL1. The effect of these SNPs is independent of classical prognostic factors and there is no heterogeneity between cohorts. Most importantly, the association with rs715212 is noteworthy (FPRP

Suggested Citation

  • Latha Kadalayil & Sofia Khan & Heli Nevanlinna & Peter A. Fasching & Fergus J. Couch & John L. Hopper & Jianjun Liu & Tom Maishman & Lorraine Durcan & Sue Gerty & Carl Blomqvist & Brigitte Rack & Wolf, 2017. "Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01775-y
    DOI: 10.1038/s41467-017-01775-y
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